The diabetic heart is presented with high levels of both ketone bodies and fatty acids. Both classes of compounds serve as energy sources for heart; however, at the level of ketone bodies achieved in uncontrolled diabetes, ketone bodies are used in preference to fatty acid as a source of energy. A large proportion of fatty acids taken up by heart under these conditions become esterified in triglyceride. In addition, ketone bodies, either directly or indirectly, inhibit mobilization of heart triglyceride. Thus, the metabolism of ketone bodies and fatty acid are tightly linked at several levels. One effect of aberrant regulation of lipid metabolism in heart that is observed in the presence of high levels of ketone bodies is triglyceride accumulation. Triglyceride accumulation in the diabetic heart, as a result of interactions between ketone body and fatty acid utilization, contributes to the prevalence and severity of coronary artery disease and myocardial infarction in the human diabetic. Our research will explore the interactions of fatty acid and ketone body metabolism in heart to identify the regulatory mechanisms that account for preferential utilization of ketone bodies, relative to fatty acid, in heart and the increased esterification of fatty acids in ketosis. Those regulatory mechanisms will be identified by correlating results obtained from studies with isolated perfused rat heart, isolated mitochondria and purified enzymes involved in the initial steps of fatty acid oxidation in the mitochondria.